This invention relates to a method for treatment of skin malignancies and pre-malignant skin lesions, including squamous cell carcinoma, basal cell carcinoma, actinic keratosis, and leukoplakia. This invention also relates to a method for treatment of psoriasis and herpes zoster.
Basal cell carcinomas, which may appear as small, shiny, firm nodules or ulcerated crusted lesions on the skin, are generally treated by electrodesiccation and curettage, surgical excision or X-ray therapy. In about 5% of cases, recurrences occur. Such recurrences are treated typically with further excision or Moh's chemosurgery, i.e., microscopically controlled excision after chemical fixation of the tissue.
Squamous cell carcinoma arises from the malpighian cells of the epithelium. The tumor generally begins as a small red papule or plaque with a scaly or crusted surface. Subsequently, it becomes nodular. Eventually, the lesion ulcerates and invades the underlying tissue. As with basal cell carcinoma, squamous cell carcinoma is heated with electrodesiccation and curettage, surgical excision or X-ray therapy.
Pecancerous keratotic lesions, actinic keratoses, are the frequent consequence of many years of overexposure exposure to sunlight. The keratoses are usually hard, and gray to dark in color. Such lesions are generally treated by topical application of fluorouracil (5-fluorouracil). However, if the lesions become malignant, topical application of fluorouracil is not recommended as the rate of recurrence is unacceptably high with such therapy.
Leukoplakia, hyperkeratinization of the oral mucosa, is generally believed to result from several factors, local or systemic, acting independently or in combination, such as: tobacco, alcohol, chronic irritation from such causes as cheek biting, ill-fitting dentures, sharp, broken or worn-down teeth or spicy foods, syphilis, vitamin deficiency, hormonal changes and Candida albicans. Leukoplakia lesions vary from a small, well-localized white patch to a diffuse area involving much of the oral mucosa, and from a smooth, flat, or slightly elevated, translucent white plaque to a thick, fissured papillomatous lesion that is firm to palpation. Treatment of leukoplakia generally comprises initial removal or elimination of any recognizable irritating factors, such as tobacco or faulty restoration or prosthetic devices, to chemical irritants, and total excision or cauterization of the localized lesions. Large lesions may be removed by a series of "stripping" operations. The patient should additionally be re examined periodically and any legions subsequently located biopsied because of the pre-cancerous nature of the disease. Additionally, leukoplakia may be involved in lesions of the vulva and anus. When involved with the vulva, leukoplakia is treated by total vulvectomy.
Psoriasis is characterized by skin lesions which are sharply demarcated, usually non-pruritic, erythematous papules or plaques covered with overlappinq, silvery or lightly opalescent, shiny scales. The typical course of psoriasis is chronic remission and recurrence, which vary in frequency and duration. Psoriasis varies in severity from one or two lesions to a widespread dermatosis, to psoriatic arthritis or exfoliation. Treatment depends upon the extent and severity of the involvement. The simplest form of treatment, topical application of lubricants, keratolytics and corticosteroids, is initially employed. Systemic antimetabolites should be used only in severe skin or joint involvement because of their potential adverse effects. Exposure to ultraviolet light has been found helpful in the treatment of psoriasis. Methotrexate taken orally is generally an effective treatment in severe disabling psoriasis which has not responded to topical therapy. However, because of the toxicity of methotrexate, hematological, renal and hepatic functions of the patient must be carefully monitored.
Herpes zoster is a virus-related, acute CNS infection involving primarily the dorsal root ganglia, and characterized by vesicular eruption and neuralgic pain in the cutaneous area supplied by peripheral sensory nerves arising in the affected root qanqlia. Herpes zoster may be activated by local lesions or by systemic disease, among other reasons. Prodromal symptoms of chills and fever, malaise and GI disturbances may be present for three or four days before the distinctive features of the disease develop. On about the fourth or fifth day, characteristic crops of vesicles on an erythematous base appear, following the cutaneous distribution of one or more posterior root ganglia. There is no specific treatment for herpes zoster. Early systemic application of a corticosteroid, however, generally relieves pain.
It would thus be desirable to provide a method for treatment of malignant and pre-malignant skin lesions, which comprises topical administration of an effective agent.
It would also be desirable to provide an effective method for treatment of malignant and pre-malignant skin lesions which employs topical application of a non-toxic agent.
It would also be desirable to provide an effective method for treatment of psoriasis comprising topical administration of a non-toxic and relatively non-antigenic agent.
It would further be desirable to provide a method for treatment of herpes zoster comprising topical administration of an effective, therapeutic agent.
Human interferon is known to protect cells against viral infection. Human interferon is produced by cells in reaction to the presence of specific inducers, such as viruses. It may be produced in vivo by the cells of living organisms, or it may be produced in vitro by cell cultures in response to the presence of the inducer. There are now known to be three main varieties of human interferon: leukocyte (.alpha.), fibroblast (.beta.) and inunune (.gamma.). Additionally, there are also known to be several subvarieties of human leukocyte (.alpha.) and fibroblast (.beta.) interferon.
Human interferon is nontoxic and relatively nonantigenic in humans. It is an effective agent against a broad spectrum of viruses, including herpes simplex virus. For example, U.S. Pat. No. 4,061,538 (Dorner et al.) and U.S. Pat. No. 4,184,917 (Dorner et al.) disclose a method of treating herpes simplex viral infections by administering structurally modified interferons to the patient. The method of administration disclosed in the Dorner patents is systemic. Several published reports also disclose treatment of herpetic eye infections by topical administration of human interferon. For example, see D. Naumann-Haefelin et al. in Infection and Immunicyt, 17:458 (1977) and B. R. Jones et al. in Lancet ii:128 (976).
It has also been recently discovered that nonionic surface active agents (such as are employed as spermicides in vaginal contraceptives) are effective in treatment of viral skin diseases. For example, in Asculai, S. S. et al; Antimicrobial Agents and Chemotherapy, 13:686 (1978), it is reported that certain nonionic surface active agents rapidly reduce the infectivity of herpes simplex viruses (HSV-1) and HSV-2) in vitro. The nonionic surface active agents which inactivated the infectivity of the viruses were those possessing ether or amide linkages between the hydrophilic and the hydrophobic portions of the molecule. See also U.S. Pat. No. 4,020,183 (Asculai et al.) and U.S. Pat. No. 4,139,630 (Asculai et al.) The therapeutic effect of such nonionic surfactants was attributed in part to their potential to dissolve the lipid-containing envelope of the virus. The non-ionic surfactants were also reported to partially destroy the nucleocapsid of the virus.
Topical administration of human interferon and activiral surfactants, preferably a nonionic surfactant, in the treatment of herpes simplex legions (both HSV-1 and HSV-2) has been disclosed in co-pending and co-assigned U.S. patent application Ser. No. 311,035 (Asculai et al.), filed Oct. 3, 1981.
Accordingly, it is an object of the present invention to provide a method for treatment of malignant and pre-malignant skin lesions, herpes zoster and psoriasis.
It is also an object of the present invention to provide a method of treatment of skin malignancies and pre-malignant lesions, herpes zoster and psoriasis which comprises topical treatment of the affected skin area with a pharmaceutical composition.
It is another object of this invention to provide a method for treatment of malignant and pre-malignant skin lesions by topical administration of a nontoxic pharmaceutical composition.
It is a further object of this invention to provide a method for treatment of skin lesions produced by squamous cell carcinoma, basal cell carcinoma, actinic keratosis, leukoplakia, psoriasis and herpes zoster which comprises administration of a relatively nonantigenic pharmaceutical preparation.